HEXST: Hexagonal Shifted-Window Transformer for Spatial Transcriptomics Gene Expression Prediction

Spatial transcriptomics offers spatially resolved gene expression profiling within tissue sections, but its cost and limited throughput hinder large-scale deployment. To extend this capability to routine practice, recent computational methods aim to infer spatial gene expression directly from ubiquitous hematoxylin and eosin-stained histology slides. However, most existing models assume Cartesian or geometry-agnostic locality, despite the hexagonal sampling of widely used spot-array platforms, and point-wise regression objectives often yield over-smoothed gene expression profiles, obscuring gene-specific spatial heterogeneity. To address these, we propose HEXST, a geometry-aligned Transformer for spatial gene expression prediction from histology. HEXST operates directly on hexagonal spot coordinates to enable efficient local-to-global contextual modeling via tailored shifted-window attention mechanism and hexagonal rotary positional encoding. To enhance gene-wise spatial contrast, HEXST complements point-wise regression with a contrast-sensitive differential objective and transcriptomic priors from a pretrained single-cell foundation model during training. Across seven spatial transcriptomics datasets, HEXST consistently outperforms state-of-the-art models, providing accurate and robust spatial gene expression predictions while preserving gene-wise contrast and spatial heterogeneity.

Hierarchical Classification for Improved Histopathology Image Analysis

Whole-slide image analysis is essential for diagnostic tasks in pathology, yet existing deep learning methods primarily rely on flat classification, ignoring hierarchical relationships among class labels. In this study, we propose HiClass, a hierarchical classification framework for improved histopathology image analysis, that enhances both coarse-grained and fine-grained WSI classification. Built based upon a multiple instance learning approach, HiClass extends it by introducing bidirectional feature integration that facilitates information exchange between coarse-grained and fine-grained feature representations, effectively learning hierarchical features. Moreover, we introduce tailored loss functions, including hierarchical consistency loss, intra- and inter-class distance loss, and group-wise cross-entropy loss, to further optimize hierarchical learning. We assess the performance of HiClass on a gastric biopsy dataset with 4 coarse-grained and 14 fine-grained classes, achieving superior classification performance for both coarse-grained classification and fine-grained classification. These results demonstrate the effectiveness of HiClass in improving WSI classification by capturing coarse-grained and fine-grained histopathological characteristics.

Pathology-Informed Latent Diffusion Model for Anomaly Detection in Lymph Node Metastasis

Anomaly detection is an emerging approach in digital pathology for its ability to efficiently and effectively utilize data for disease diagnosis. While supervised learning approaches deliver high accuracy, they rely on extensively annotated datasets, suffering from data scarcity in digital pathology. Unsupervised anomaly detection, however, offers a viable alternative by identifying deviations from normal tissue distributions without requiring exhaustive annotations. Recently, denoising diffusion probabilistic models have gained popularity in unsupervised anomaly detection, achieving promising performance in both natural and medical imaging datasets. Building on this, we incorporate a vision-language model with a diffusion model for unsupervised anomaly detection in digital pathology, utilizing histopathology prompts during reconstruction. Our approach employs a set of pathology-related keywords associated with normal tissues to guide the reconstruction process, facilitating the differentiation between normal and abnormal tissues. To evaluate the effectiveness of the proposed method, we conduct experiments on a gastric lymph node dataset from a local hospital and assess its generalization ability under domain shift using a public breast lymph node dataset. The experimental results highlight the potential of the proposed method for unsupervised anomaly detection across various organs in digital pathology. Code: https://github.com/QuIIL/AnoPILaD.

VideoPath-LLaVA: Pathology Diagnostic Reasoning Through Video Instruction Tuning

We present VideoPath-LLaVA, the first large multimodal model (LMM) in computational pathology that integrates three distinct image scenarios, single patch images, automatically keyframe-extracted clips, and manually segmented video pathology images, to mimic the natural diagnostic process of pathologists. By generating detailed histological descriptions and culminating in a definitive sign-out diagnosis, VideoPath-LLaVA bridges visual narratives with diagnostic reasoning. Central to our approach is the VideoPath-Instruct dataset, comprising 4278 video and diagnosis-specific chain-of-thought instructional pairs sourced from educational histopathology videos on YouTube. Although high-quality data is critical for enhancing diagnostic reasoning, its creation is time-intensive and limited in volume. To overcome this challenge, we transfer knowledge from existing single-image instruction datasets to train on weakly annotated, keyframe-extracted clips, followed by fine-tuning on manually segmented videos. VideoPath-LLaVA establishes a new benchmark in pathology video analysis and offers a promising foundation for future AI systems that support clinical decision-making through integrated visual and diagnostic reasoning. Our code, data, and model are publicly available at https://github.com/trinhvg/VideoPath-LLaVA.

VLEER: Vision and Language Embeddings for Explainable Whole Slide Image Representation

Recent advances in vision-language models (VLMs) have shown remarkable potential in bridging visual and textual modalities. In computational pathology, domain-specific VLMs, which are pre-trained on extensive histopathology image-text datasets, have succeeded in various downstream tasks. However, existing research has primarily focused on the pre-training process and direct applications of VLMs on the patch level, leaving their great potential for whole slide image (WSI) applications unexplored. In this study, we hypothesize that pre-trained VLMs inherently capture informative and interpretable WSI representations through quantitative feature extraction. To validate this hypothesis, we introduce Vision and Language Embeddings for Explainable WSI Representation (VLEER), a novel method designed to leverage VLMs for WSI representation. We systematically evaluate VLEER on three pathological WSI datasets, proving its better performance in WSI analysis compared to conventional vision features. More importantly, VLEER offers the unique advantage of interpretability, enabling direct human-readable insights into the results by leveraging the textual modality for detailed pathology annotations, providing clear reasoning for WSI-level pathology downstream tasks.

Patch Stitching Data Augmentation for Cancer Classification in Pathology Images

Computational pathology, integrating computational methods and digital imaging, has shown to be effective in advancing disease diagnosis and prognosis. In recent years, the development of machine learning and deep learning has greatly bolstered the power of computational pathology. However, there still remains the issue of data scarcity and data imbalance, which can have an adversarial effect on any computational method. In this paper, we introduce an efficient and effective data augmentation strategy to generate new pathology images from the existing pathology images and thus enrich datasets without additional data collection or annotation costs. To evaluate the proposed method, we employed two sets of colorectal cancer datasets and obtained improved classification results, suggesting that the proposed simple approach holds the potential for alleviating the data scarcity and imbalance in computational pathology.

USegMix: Unsupervised Segment Mix for Efficient Data Augmentation in Pathology Images

In computational pathology, researchers often face challenges due to the scarcity of labeled pathology datasets. Data augmentation emerges as a crucial technique to mitigate this limitation. In this study, we introduce an efficient data augmentation method for pathology images, called USegMix. Given a set of pathology images, the proposed method generates a new, synthetic image in two phases. In the first phase, USegMix constructs a pool of tissue segments in an automated and unsupervised manner using superpixels and the Segment Anything Model (SAM). In the second phase, USegMix selects a candidate segment in a target image, replaces it with a similar segment from the segment pool, and blends them by using a pre-trained diffusion model. In this way, USegMix can generate diverse and realistic pathology images. We rigorously evaluate the effectiveness of USegMix on two pathology image datasets of colorectal and prostate cancers. The results demonstrate improvements in cancer classification performance, underscoring the substantial potential of USegMix for pathology image analysis.

NucleiMix: Realistic Data Augmentation for Nuclei Instance Segmentation

Nuclei instance segmentation is an essential task in pathology image analysis, serving as the foundation for many downstream applications. The release of several public datasets has significantly advanced research in this area, yet many existing methods struggle with data imbalance issues. To address this challenge, this study introduces a data augmentation method, called NucleiMix, which is designed to balance the distribution of nuclei types by increasing the number of rare-type nuclei within datasets. NucleiMix operates in two phases. In the first phase, it identifies candidate locations similar to the surroundings of rare-type nuclei and inserts rare-type nuclei into the candidate locations. In the second phase, it employs a progressive inpainting strategy using a pre-trained diffusion model to seamlessly integrate rare-type nuclei into their new environments in replacement of major-type nuclei or background locations. We systematically evaluate the effectiveness of NucleiMix on three public datasets using two popular nuclei instance segmentation models. The results demonstrate the superior ability of NucleiMix to synthesize realistic rare-type nuclei and to enhance the quality of nuclei segmentation and classification in an accurate and robust manner.

Benchmarking Pathology Foundation Models: Adaptation Strategies and Scenarios

In computational pathology, several foundation models have recently emerged and demonstrated enhanced learning capability for analyzing pathology images. However, adapting these models to various downstream tasks remains challenging, particularly when faced with datasets from different sources and acquisition conditions, as well as limited data availability. In this study, we benchmark four pathology-specific foundation models across 14 datasets and two scenarios-consistency assessment and flexibility assessment-addressing diverse adaptation scenarios and downstream tasks. In the consistency assessment scenario, involving five fine-tuning methods, we found that the parameter-efficient fine-tuning approach was both efficient and effective for adapting pathology-specific foundation models to diverse datasets within the same downstream task. In the flexibility assessment scenario under data-limited environments, utilizing five few-shot learning methods, we observed that the foundation models benefited more from the few-shot learning methods that involve modification during the testing phase only. These findings provide insights that could guide the deployment of pathology-specific foundation models in real clinical settings, potentially improving the accuracy and reliability of pathology image analysis. The code for this study is available at: https://github.com/QuIIL/BenchmarkingPathologyFoundationModels.

MECFormer: Multi-task Whole Slide Image Classification with Expert Consultation Network

Whole slide image (WSI) classification is a crucial problem for cancer diagnostics in clinics and hospitals. A WSI, acquired at gigapixel size, is commonly tiled into patches and processed by multiple-instance learning (MIL) models. Previous MIL-based models designed for this problem have only been evaluated on individual tasks for specific organs, and the ability to handle multiple tasks within a single model has not been investigated. In this study, we propose MECFormer, a generative Transformer-based model designed to handle multiple tasks within one model. To leverage the power of learning multiple tasks simultaneously and to enhance the model's effectiveness in focusing on each individual task, we introduce an Expert Consultation Network, a projection layer placed at the beginning of the Transformer-based model. Additionally, to enable flexible classification, autoregressive decoding is incorporated by a language decoder for WSI classification. Through extensive experiments on five datasets involving four different organs, one cancer classification task, and four cancer subtyping tasks, MECFormer demonstrates superior performance compared to individual state-of-the-art multiple-instance learning models.